Remotely controlled steerable sheath improves result and procedural parameters of atrial fibrillation ablation with magnetic navigation.

AIMS: The magnetic navigation (MN) system may be coupled with a new advancement system that fully controls both the catheter and a robotic deflectable sheath (RSh) or with a fixed-curve sheath and a catheter-only advancement system (CAS). We aimed to compare these approaches for atrial fibrillation (AF) ablation. METHODS AND RESULTS: Atrial fibrillation ablation patients (45, 23 paroxysmal and 22 persistent) performed with MN-RSh (RSh group) were compared with a control group (37, 18 paroxysmal and19 persistent) performed with MN-CAS (CAS group). Setup duration was measured from the procedure's start to operator transfer to control room. Ablation step duration was defined as the time from the beginning of the first radiofrequency (RF) pulse to the end of the last one and was separately acquired for the left and the right pulmonary vein (PV) pairs. Clinical characteristics, left atrial size, and AF-type distribution were similar between the groups. Setup duration as well as mapping times was also similar. Ablation step duration for the left PVs was similar, but was shorter for the right PVs in RSh group (46 ± 9 vs. 63 ± 12 min, P < 0.0001). Radiofrequency delivery time (34 ± 9 vs. 40 ± 11 min, P = 0.007) and procedure duration (227 ± 36 vs. 254 ± 62 min, P = 0.01) were shorter in RSh group. No complication occurred in RSh group. During follow-up, there were five recurrences (11%) in RSh group and 11 (29%) in CAS group (P = 0.027). CONCLUSION: The use of the RSh for AF ablation with MN is safe and improves outcome. Right PV isolation is faster, RF delivery time and procedure time are reduced.

Akt down-regulates ERK1/2 nuclear localization and angiotensin II-induced cell proliferation through PEA-15.

Angiotensin II (AngII) type 1 receptors (AT1) regulate cell growth through the extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol 3-kinase (PI3K) pathways. ERK1/2 and Akt/protein kinase B, downstream of PI3K, are independently activated but both required for mediating AngII-induced proliferation when expressed at endogenous levels. We investigate the effect of an increase in the expression of wild-type Akt1 by using Chinese hamster ovary (CHO)-AT1 cells. Unexpectedly, Akt overexpression inhibits the AT1-mediated proliferation. This effect could be generated by a cross-talk between the PI3K and ERK1/2 pathways. A functional partner is the phosphoprotein enriched in astrocytes of 15 kDa (PEA-15), an Akt substrate known to bind ERK1/2 and to regulate their nuclear translocation. We report that Akt binds to PEA-15 and that Akt activation leads to PEA-15 stabilization, independently of PEA-15 interaction with ERK1/2. Akt cross-talk with PEA-15 does not affect ERK1/2 activation but decreases their nuclear activity as a result of the blockade of ERK1/2 nuclear accumulation. In response to AngII, PEA-15 overexpression displays the same functional consequences on ERK1/2 signaling as Akt overactivation. Thus, Akt overactivation prevents the nuclear translocation of ERK1/2 and the AngII-induced proliferation through interaction with and stabilization of endogenous PEA-15.

Akt is a major downstream target of PI3-kinase involved in angiotensin II-induced proliferation.

Different signal transduction cascades have been implicated in angiotensin II (Ang II)-mediated cell growth, such as the extracellular signal-regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol 3-kinase (PI3K) pathways. To identify the downstream targets of PI3K involved in Ang II-induced proliferation, we used both rat aortic smooth muscle (RASM) cells and a CHO cell line stably expressing the rat AT1A receptor. The ERK1/2 and PI3K pathways are independently activated and implicated in Ang II-mediated DNA synthesis and cell number increase in these 2 cell lines. In addition, a specific inhibitor of Akt inhibited Ang II-induced Akt phosphorylation, DNA synthesis and proliferation in CHO-AT1A or RASM cells. A dominant-negative mutant of Akt was also found to selectively block Ang II-induced proliferation of CHO-AT1A cells. To further elucidate the signaling events leading to Akt activation, we used an AT1 receptor mutant (AT1AD74E), deficient for Gq protein coupling, and the intracellular calcium chelator BAPTA-AM. Although altered Akt and ERK1/2 activation was observed in the CHO-AT1AD74E cell line, blockade of intracellular calcium elevation did not affect phosphorylation of these kinases. These results provide the first evidence of a specific and necessary role of Akt in Ang II-induced proliferation through a Gq protein-dependent calcium-independent pathway.